ArticleJournal of the American Heart Association2015
Identification of a Novel Heart-Liver Axis: Matrix Metalloproteinase-2 Negatively Regulates Cardiac Secreted Phospholipase A2 to Modulate Lipid Metabolism and Inflammation in the Liver.
Article in Journal of the American Heart Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Unifying and unique roles of non-coding RNA biomarkers in liver and heart fibrosis.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Review
- Diabetes and its complications: molecular mechanisms, prevention and treatment.Signal transduction and targeted therapy · 2026Review
- Link between Metabolic Dysfunction-Associated Steatotic Liver Disease and Cardiovascular Diseases.Research (Washington, D.C.) · 2026Review
- Identification of Plasma Lipidomic Signatures Associated with Coronary Plaque Vulnerability.Journal of cardiovascular translational research · 2025Article
- The Cardiohepatic Axis in Metabolic Disease: Liver to Heart.JACC. Basic to translational science · 2025Review
- Decoding the Liver-Heart Axis in Cardiometabolic Diseases.Circulation research · 2025Review
- Correlation between cardiac and hepatic native T1 value and myocardial late gadolinium enhancement in children with Kawasaki disease.Quantitative imaging in medicine and surgery · 2025Article
- Lysophosphatidylcholine induced by fat transplantation regulates hyperalgesia by affecting the dysfunction of ACC perineuronal nets.iScience · 2024Article
- An integrated multi-omics analysis of the effects of the food processing-induced contaminant 2-monochloropropane-1,3-diol (2-MCPD) in rat heart.Archives of toxicology · 2024Article
- Neural Circuits Underlying Reciprocal Cardiometabolic Crosstalk: 2023 Arthur C. Corcoran Memorial Lecture.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Low-grade inflammation is associated with a heterogeneous lipoprotein subclass profile in an apparently healthy population sample.Lipids in health and disease · 2023Article
- The Network between Heart and Liver from the View of Persian Medicine Versus Conventional Medicine.Galen medical journal · 2023Article
- Extracellular vesicle-mediated bidirectional communication between heart and other organs.American journal of physiology. Heart and circulatory physiology · 2022Review
- Defining the Roles of Cardiokines in Human Aging and Age-Associated Diseases.Frontiers in aging · 2022Review
- A Metalloproteinase Induces an Inflammatory Response in Preadipocytes with the Activation of COX Signalling Pathways and Participation of Endogenous Phospholipases ABiomolecules · 2021Article
- Matrix Metalloproteinases and Arterial Hypertension: Role of Oxidative Stress and Nitric Oxide in Vascular Functional and Structural Alterations.Biomolecules · 2021Review
- Targeting MMP-Regulation of Inflammation to Increase Metabolic Tolerance to COVID-19 Pathologies: A Hypothesis.Biomolecules · 2021Article
- Hepatocardiac or Cardiohepatic Interaction: From Traditional Chinese Medicine to Western Medicine.Evidence-based complementary and alternative medicine : eCAM · 2021Review
- Cardiac myocyte KLF5 regulates body weight via alteration of cardiac FGF21.Biochimica et biophysica acta. Molecular basis of disease · 2019Article
- Emerging pathways of communication between the heart and non-cardiac organs.Journal of biomedical research · 2019Article
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundEndocrine functions of the heart have been well established. We investigated the hypothesis that cardiac secretion of a unique phospholipase A2 recently identified by our laboratory (cardiac secreted phospholipase A2 [sPLA2]) establishes a heart-liver endocrine axis that is negatively regulated by matrix metalloproteinase-2 (MMP-2). METHODS AND
resultsIn Mmp2(-/-) mice, cardiac (but not hepatic) sPLA2 was elevated, leading to hepatic inflammation, immune cell infiltration, dysregulation of the sterol regulatory element binding protein-2 and liver X receptor-α pathways, abnormal transcriptional responses to dietary cholesterol, and elevated triglycerides in very low-density lipoprotein and in the liver. Expression of monocyte chemoattractant protein-3, a known MMP-2 substrate, was elevated at both mRNA and protein levels in the heart. Functional studies including in vivo antibody neutralization identified cardiac monocyte chemoattractant protein 3 as a possible agonist of cardiac sPLA2 secretion. Conversely, systemic sPLA2 inhibition almost fully normalized the cardiohepatic phenotype without affecting monocyte chemoattractant protein-3. Finally, wild-type mice that received high-performance liquid chromatography-isolated cardiac sPLA2 from Mmp2(-/-) donors developed a cardiohepatic gene expression profile similar to that of Mmp2(-/-) mice.
conclusionsThese findings identified the novel MMP-2/cardiac sPLA2 pathway that endows the heart with important endocrine functions, including regulation of inflammation and lipid metabolism in the liver. Our findings could also help explain how MMP2 deficiency leads to cardiac problems, inflammation, and metabolic dysregulation in patients.
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